To determine antibody responses to small doses of human diploid cell rabies vaccine (HDCV), rabies antibody titers were determined in 124 volunteers who were vaccinated with 1 of 5 primary preexposure regimens. In a 6th group of 47 persons previously vaccinated with duck embryo rabies vaccine (DEV), the booster response was evaluated after a 0.1 ml dose of intradermal i.d. HDCV. Persons in all 5 groups undergoing primary immunization received 3 doses of vaccine, 1 each on days 0, 7 and 28. The dose and route of vaccination for the 5 groups included 1 ml i.m., 0.1 ml i.d. (2 subgroups), 0.1 ml s.c. and 0.25 ml s.c. Adequate titers developed in all persons, irrespective of the route or quantity of vaccine. The geometric mean titers (IU/ml) on day 49 in those receiving primary regimens were 12.87 (1.0 ml i.m.), 7.44 (0.1 ml i.d. by syringe), 3.05 (0.1 ml by jet injector), 3.17 (0.1 ml s.c. and 6.47 (0.25 ml s.c.). Titers on day 90, while lower, were still acceptable. Adequate antibody titers developed in all persons previously vaccinated with DEV after a single 0.1-ml i.d. dose of HDCV; higher titers developed at day 7 in those who had shown an adequate response to DEV in the past. Thus, HDCV may be used i.d. or s.c. for primary preexposure rabies prophylaxis and i.d. for booster immunization.